Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines induce a number of changes in lipid metabolism that can produce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently discovered cytokine, has been suggested to play a role in the cancer cachexia syndrome through its ability to decrease lipoprotein lipase (LPL) activity. This study explores the mechanism by which LIP decreases LPL activity in cultured adipocytes and determines its effects on fatty acid synthesis and lipolysis to see if it shares the same catabolic effects on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent decrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokines are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL activity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF caused a small increase in lipolysis, whereas TNF increased lipolysis by greater than 2-fold. These results demonstrate that the catabolic effects of LIF are weaker than those of TNF and are predominantly directed toward decreasing LPL activity, which may contribute to the hyperlipidemia associated with infection, inflammation, and cancer.
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PMID:Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes. 801 46

Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To answer that question, the effect of FFA/triacylglycerol on plasma PAI-1 was examined. Ten healthy male volunteers were studied for 6 h during infusion of triacylglycerol [1.5 ml/min]/heparin [0.2 IU/(kg.min)] (LIP; n=10), saline only (SAL; n=10), and saline/heparin (HEP; n=5). Plasma insulin concentrations were kept constant at approximately 35 pmol/l by intravenous somatostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA approximately 3- (p < 0.001) and approximately 8- (p < 0.000001) fold, respectively, within 90 min. Baseline plasma PAI-1 measured by a bio-immunoassay was similar in HEP (11.4 +/- 2.8 ng/ml), SAL (16.6 +/- 3.6 ng/ml), and LIP studies (15.2 +/- 3.4 ng/ml). Since studies were initiated in the morning, PAI-1 decreased (p < 0.025) over time following its normal diurnal variation to 6.4 +/- 2.0 ng/ml and 4.0 +/- 2.4 ng/ml at 360 min in SAL and HEP, respectively. During LIP, however, PAI-1 increased to approximately 2.6 fold higher levels than during SAL at 360 min (16.4 +/- 4.0 ng/ml, p < 0.01). While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p = 0.02) with those seen for PAI-1. This suggests that hyperlipidemia independent of insulin and plasma glucose levels stimulates vascular tissue and in turn might induce an increase in plasma PAI-1. PAI-1 then could contribute to the development of atherothrombotic vascular disease.
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PMID:Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. 1295 10

There is a growing interest in the screening of antihyperlipidemic activity and the present study deals with the screening of a polyherbomineral formulation (AF-LIP) which possess many important ingredients reported to have antihyperlipidemic potency. Acute antihyperlipidemic activity was evaluated by using Triton WR-1339 (100 mg kg(-1)) and chronic, induced by high fat diet. Total Cholesterol (TC), triglycerides (TG), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) and Very Low Density Lipoproteins (VLDL) were examined in addition to HMG-CoA reductase enzyme activity and fecal cholesterol excretion. In Triton WR-1339 (acute model) at the dose of 400 mg kg(-1), AF-LIP significantly lowered TC, TG, very Low Density Lipoproteins Cholesterol (VLDL-C), Low Density Lipoproteins Cholesterol (LDL-C) levels with simultaneous increase in High Density Lipoproteins Cholesterol (HDL-C) levels (p < 0.01) at 6 and 24 h. Also there was significant reduction in TC and LDL-C levels at 48 h at the dose of 400 mg kg(-1). In chronic model also at the dose of 100, 200 and 400 mg kg(-1), AF-LIP significantly reduced (p < 0.001) TC and LDL-C levels with increase in HDL-C levels. TG and VLDL-C levels were also not much affected. HMG-CoA reductase enzyme activity when estimated was not much decreased. Also AF-LIP showed significant reduction in atherogenic index (p < 0.01) with significant increase in HDL/TC ratio (p < 0.01). Fecal cholesterol excretion was significantly enhanced (p < 0.01) in all the test doses of AF-LIP. AF-LIP may be beneficial for the treatment of atherosclerosis, since atherosclerosis is one of the secondary complications of hyperlipidemia.
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PMID:Evaluation of antihyperlipidemic potency of a polyherbomineral formulation (AF-LIP) in experimental animal models. 2489 88